PROJECT ABSTRACT Dementia and Overactive Bladder (OAB) are one of the most common comorbid conditions affecting older patients. Pharmacological management of OAB involves use of antimuscarinic drugs. Although antimuscarinics are effective, they vary in their safety and tolerability profiles due to differing selectivity for muscarinic receptor subtypes. Some of the antimuscarinics like oxybutynin, tolterodine, trospium, fesoterodine are non-selective as they have affinity for all muscarinic receptors, and others like darifenacin and solifenacin are selective due to their high affinity for M2/M3 receptors that are responsible for bladder contraction. Central adverse effects of antimuscarinics are a significant concern in dementia patients as these patients suffer from progressive cognitive decline due to damage to the cholinergic neurons system, and antimuscarinics can worsen the disease state and can adversely affect patient outcomes. Furthermore, studies have consistently found strong evidence of increased medication-related morbidity and mortality due to anticholinergic use. However, very limited comparative safety data exists regarding antimuscarinics in older patients, and even little is known about the safety of OAB medications in dementia patients. The goal of this population-based research is to evaluate adverse outcomes of antimuscarinics in patients with dementia and OAB. Understanding the safety profile of antimuscarinics is critical for providers to enable them to make informed decisions regarding antimuscarinic use in this vulnerable population. Therefore, the specific objectives of the research are to: (1) examine the prevalence and predictors of antimuscarinic use among older dementia patients with OAB; (2) evaluate the risk of falls/fractures and all-cause hospitalization due to antimuscarinic use among older dementia patients with OAB; and (3) assess the risk of all-cause mortality due to antimuscarinic use among older dementia patients with OAB. Antimuscarinics will be classified as non-selective and selective agents. The study will test the hypotheses that there is a greater risk for medication-related morbidity (falls/fractures and all-cause hospitalization) and all-cause mortality due to non-selective antimuscarinics as compared to selective antimuscarinics among older patients with OAB and dementia. This study will involve a cohort of patients 65 years or older with dementia and comorbid OAB based on multi-year Medicare claims data involving Parts A, B, and D. The study will involve propensity score matched cohort design to adjust for the selection bias across antimuscarinic classes within the multivariate context of the Andersen Behavioral Model. The robust Cox proportional hazards models involving a robust sandwich estimate will be used to account for the clustering within matched sets. Multiple sensitivity analyses including nested case-control design will be conducted to assess the robustness of findings. The study findings will provide much needed comparative safety data on antimuscarinics in the older patients with complex and comorbid conditions. The findings will have significant clinical and policy implications for safe medication practices in patients with dementia.